Approximately half of human melanomas originate from precursor melanocytic proliferations termed melanocytic nevi. However, most melanocytic nevi do not undergo malignant transformation, but rather remain stable throughout life or disappear. To understand the determinants of melanocyte transformation, especially as they apply to the development of primary human melanoma from melanocytic nevus precursor lesions, we are planning a patient-based study with two goals. One is to define the clinical characteristics of early primary melanomas with greater precision, using skin epiluminescent microscopy, or dermascopy, to visualize specific structures that can be correlated with lesional histopathology. The other is to sample and immortalize melanocytes from clinically benign melanocytic nevi, in order to study signalling pathways and gene expression in these cells to gain more insight into a common first step in the process of melanocyte transformation. One potential benefit of this study is that the clinical knowledge gained about early primary melanomas, combined with the development of techniques to immortalize adult human melanocytes, may make it possible in a subsequent study to obtain and expand cells from these early malignant lesions to understand this stage of malignant transformation. This is especially important since most human melanoma cell lines used today are derived either from advanced primary tumors or metastases, and have little detailed clinical annotation associated with them.